Research progress on the mechanisms and clinical applications of neuromodulation techniques for intervening in...

Post-stroke interhemispheric inhibitory imbalance acts as one of the major contributing pathological factors driving motor impairment, rather than a universal primary pathological mechanism across all stroke subtypes. This narrative review systematically summarizes preclinical and clinical neuromodulation interventions including optogenetic manipulation and transcranial magnetic stimulation, grounded in the interhemispheric inhibition (IHI) theory and bimodal balance-recovery framework. We elaborate how these techniques restore excitatory/inhibitory (E/I) homeostasis via regulating neurotransmitter concentrations, modifying receptor expression, and modulating targeted transcallosal neuronal circuits, while explicitly acknowledging inconsistent research findings across measurement modalities, stroke recovery stages and patient subgroups. We further integrate quantitative clinical trial data, effect sizes and evidence grading to analyze current clinical translation status of repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and continuous theta-burst stimulation (cTBS). Critical unresolved challenges include translational gaps between cell-specific optogenetic mechanisms and human non-invasive brain stimulation (NIBS), heterogeneous patient responses, and lack of unified quantitative thresholds defining pathological interhemispheric imbalance. Finally, we propose prospective research directions covering multi-network targeted modulation, multimodal predictive biomarkers, combined pharmacology-neuromodulation strategies and large stratified randomized controlled trials to advance precision individualized stroke neurorehabilitation.